Lurasidone [chemical name: (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclo-hexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione] of the following formula is a novel psychotropic agent, which is characteristic of a high affinity for dopamine D2, serotonin 5-HT1A, 5-HT2A, 5-HT7, and noradrenaline α2C receptors and of minimal to no affinity for histamine H1 and muscarinic M1 receptors. Lurasidone possesses antipsychotic effects, antidepressant- or anxiolytic-like effects, and pro-cognitive effects with potentially reduced liability for extrapyramidal and CNS depressant side effects, which is expected to be used for the treatment of schizophrenia and bipolar disorder (Japan Patent Application JP-5(1993)-17440 A; J M Meyer et al. Exp Opin Invest Drugs 18(11): 1715-1726 (2009)).

Metabotropic glutamate receptors (mGluRs) are subclassified into three groups, the group I mGluRs (mGluR1 and mGluR5), the group II mGluRs (mGluR2 and mGluR3) and the group III mGluRs (mGluR4, mGluR6, mGluR7 and mGluR8). The group II mGluRs, mGluR2 and mGluR3, have emerged as exciting and well-validated targets for novel therapeutic agents used for treating psychiatric disorders (J P Conn et al., Neuropsychopharmacol Rev 34: 248-249 (2009)). A large number of preclinical and clinical studies provide strong evidence that mGluR2/3 agonists may provide a novel approach to the treatment of anxiety disorders and schizophrenia. Recently, a novel class of compounds, known as mGluR2 positive allosteric modulaters (PAMs), has shown the efficacies in the animal models that are related with the prediction of both antipsychotic and anxiolytic activities, that are very similar to those observed with mGluR2/3 agonists. While the mGluR2/3 agonists bind to orthosteric binding site of endogenous ligand glutamate, mGluR2 PAMs bind to a site distinct from the glutamate binding site to increase the responses of mGluR2 to glutamate without activating mGluR2 directly.